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What do we learn from a Genome Wide Association Study performed on HIV-1 infected Long Term Non Progressors individuals?

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HAL Id: inserm-00622545

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What do we learn from a Genome Wide Association Study performed on HIV-1 infected Long Term Non

Progressors individuals?

Julien Guergnon, Cyril Dalmasso, Ioannis Theodorou, Agostino Riva

To cite this version:

Julien Guergnon, Cyril Dalmasso, Ioannis Theodorou, Agostino Riva. What do we learn from a Genome Wide Association Study performed on HIV-1 infected Long Term Non Progressors individ- uals?. Retrovirology, BioMed Central, 2009, 6 (Suppl 2), pp.O27. �10.1186/1742-4690-6-S2-O27�.

�inserm-00622545�

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BioMed Central

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Retrovirology

Open Access

Oral presentation

What do we learn from a Genome Wide Association Study performed on HIV-1 infected Long Term Non Progressors individuals?

Julien Guergnon*

1

, Cyril Dalmasso

2

, Ioannis Theodorou

1

, Agostino Riva

3

for the GISHEAL and PRIMO studies groups

4,5

Address: 1INSERM UMR-S 945, School of Medicine Pierre et Marie Curie, Paris, France, 2University Paris 11, Villejuif, France and Genome Institute of Singapore, Singapore, 3Department of Cytomorphology, School of Medicine, University of Cagliar, Cagliari, Italy, 4GISHEAL study group School of Medicine Pierre et Marie Curie, Paris, France; Dominique Costagliola, INSERM U720, University Pierre et Marie Curie, Paris, France and

5PRIMO study group INSERM U802, University Paris-Sud 11, Le Kremlin Bicêtre, France

* Corresponding author

Background

Previous Genome Wide Association Studies performed on Elite Controllers and control HIV-1 infected individuals have shown that the MHC locus is predominantly respon- sible for containing plasma viremia below a threshold of detection. Here we performed a GWAS on a cohort of 160 HIV-1 infected Caucasian Long Term Non Progressors (LTNP) from the EC-funded European-African ''GISHEAL'' Consortium in order to explore whether novel genetic factors could account for the LTNP pheno- type (i.e. maintenance of CD4 T cell counts >500 cells/μl and good health conditions without therapy).

Results

Frequencies of the SNPs found in LTNP were challenged vs. those of seroconverters of the French ''PRIMO'' cohort.

Most of the SNPs strongly associated to LTNP phenotype were found in the MHC region (figure 1), especially encompassing class I and class III genes. Since 6 of the 10 top SNPs are in the HLA-B region, we confirm previous studies showing that class I HLA-B27 and HLA-B57 alleles are strongly correlated to the LTNP condition. In addition, about 65% of our LTNP naturally resist to HIV disease progression independently of HLA-B27/B57; in this regard, quite strikingly, 11 over 32 SNPs with a Q-value <

0.05 are located in MHC class III region in GISHEAL LTNP cohort.

Conclusion

Thus, our findings support the concept that different MHC loci significantly contribute to long-term control of HIV disease progression in the absence of antiretroviral therapy and provide novel evidence of a seminal role of MHC class III gene polymorphisms in determining the LTNP phenotype.

from Frontiers of Retrovirology: Complex retroviruses, retroelements and their hosts Montpellier, France. 21-23 September 2009

Published: 24 September 2009

Retrovirology 2009, 6(Suppl 2):O27 doi:10.1186/1742-4690-6-S2-O27

<supplement> <title> <p>Frontiers of Retrovirology: Complex retroviruses, retroelements and their hosts</p> </title> <note>Meeting abstracts - A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1742-4690-6-S2-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1742-4690-6-S2-info.pdf</url> </supplement>

This abstract is available from: http://www.retrovirology.com/content/6/S2/O27

© 2009 Guergnon et al; licensee BioMed Central Ltd.

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